Magnesium-Doped Bioactive Glass Ameliorates Inflammation Via Alleviating Er Stress

Recent studies have revealed that endoplasmic reticulum (ER) stress-mediated macrophage polarization imbalance and proinflammatory responses under inflammatory microenvironment are closely associated with the initiation and progression of periodontitis. This study aims to utilize magnesium-doped bioactive glass micro/nano particles to regulate the inflammatory microenvironment by alleviating ER stress in macrophages, providing a theoretical foundation for periodontal disease treatment. First, MgBG micro-nano particles with varying Mg molar contents (0MgBG, 2MgBG, 5MgBG, 10MgBG) were prepared via the sol-gel method. Comprehensive material characterization was performed to analyze the surface morphology, particle size distribution, elemental composition, and phase structure of MgBG. Subsequently, the effects of different MgBG formulations on macrophage polarization (M1/M2 phenotypes) under LPS-induced inflammatory conditions were evaluated, as well as their regulatory effects on inflammation-related proteins and gene expression. Transcriptome sequencing analysis and in vitro experiments were employed to investigate the immunomodulatory mechanisms of MgBG in macrophages. The results demonstrated that 10MgBG exerts anti-inflammatory effects by releasing bioactive Mg²⁺, promoting macrophage polarization from the M1 phenotype toward the M2 (anti-inflammatory) phenotype. Transcriptome sequencing and in vitro experiments revealed that Mg²⁺ alleviates ER stress and improves mitochondrial function by modulating calcium homeostasis, thereby ameliorating the LPS-induced inflammatory microenvironment through suppression of the PERK/eIF2α/NF-κB proinflammatory signaling pathway. MgBG micro/nano particles ameliorate the inflammatory microenvironment by alleviating endoplasmic reticulum stress and improving mitochondrial dysfunction, providing a crucial theoretical foundation for the clinical treatment of periodontitis.